Type 2 diabetes, also known as non-insulin dependent diabetes mellitus (NIDDM), is a condition in which patients generate insulin, but the insulin cannot be used effectively by the body's cells. This is primarily because the amount of insulin produced in response to rising blood sugar levels is not sufficient to allow cells to efficiently take up glucose and thus, reduce blood sugar levels.
Glucagon-like 1 peptides and glucagon-like 1 peptide analogs (collectively GLP-1) are a potential treatment for type 2 diabetes and obesity. GLP-1 induces the secretion and production of insulin, effectively reducing blood glucose levels in diabetic patients. GLP-1 also inhibits glucagon secretion, inhibits gastric emptying, enhances glucose utilization, and induces weight loss. GLP-1 may also act to prevent the B cell deterioration that occurs as diabetes progresses.
Development of an oral GLP-1 therapeutic has been extremely difficult. This is primarily due to the in vivo instability of the peptide. The high acid content and ubiquitous digestive enzymes of the digestive tract will often degrade GLP-1 before reaching the desired site of absorption. Further, GLP-1 may encounter difficulty in traversing the cells of the epithelial membrane in the small intestine to reach the bloodstream. Also, GLP-1 only remains in solution under a narrow set of conditions.
In light of the above difficulties, oral administration of GLP-1 compounds has not been feasible. GLP-1 compounds are customarily delivered by subcutaneous injection or through continuous subcutaneous infusion or continuous intravenous administration. Because patients are generally adverse to injections and time consuming infusions, patient compliance with GLP-1 administration regimens will be low.
Delivery agent molecules that interact with various active agents compounds in a non-covalent fashion to allow the compounds to cross gut membranes and yet remain therapeutically active have been disclosed in U.S. Pat. Nos. 6,663,898, 6,663,887, 6,646,162, 6,642,411, 6,627,228, 6,623,731, 6,610,329, 6,558,706, 6,525,020, 6,461,643, 6,461,545, 6,440,929, 6,428,780, 6,413,550, 6,399,798, 6,395,774, 6,391,303, 6,384,278, 6,375,983, 6,358,504, 6,346,242, 6,344,213, 6,331,318, 6,313,088, 6,245,359, 6,242,495, 6,221,367, 6,180,140, 5,541,155, 5,693,338, 5,976,569, 5,643,957, 5,955,503, 6,100,298, 5,650,386, 5,866,536, 5,965,121, 5,989,539, 6,001,347, 6,071,510, and 5,820,881; U.S. Published Application Nos. 20030232085, 20030225300, 20030198658, 20030133953, 20030078302, 20030072740, 20030045579, 20030012817, 20030008900, 20020155993, 20020127202, 20020120009, 20020119910, 20020102286, 20020065255, 20020052422, 20020040061, 20020028250, 20020013497, 20020001591, 20010039258, 20010003001; and International Published Application Nos. 2003/057650, 2003/057170, 2003/045331, 2003/045306, 2003/026582, 2002/100338, 2002/070438, 2002/069937, 02/20466, 02/19969, 02/16309, 02/15959, 02/02509, 01/92206, 01/70219, 01/51454, 01/44199, 01/34114, 01/32596, 01/32130, 00/07979, 00/59863, 00/50386, 00/47188, 00/40203, 96/30036.